关键词: Osteosarcoma TNFRSF1A necroptosis prognosis tumor immune microenvironment

Mesh : Humans Osteosarcoma / genetics mortality immunology pathology Receptors, Tumor Necrosis Factor, Type I / genetics metabolism Biomarkers, Tumor / genetics Bone Neoplasms / genetics pathology mortality immunology Prognosis Female Male Nomograms Adolescent Kaplan-Meier Estimate Gene Expression Regulation, Neoplastic Tumor Microenvironment / immunology genetics

来  源:   DOI:10.3233/CBM-230086   PDF(Pubmed)

Abstract:
UNASSIGNED: Osteosarcoma (OS) is a relatively rare malignant bone tumor in teenagers; however, its molecular mechanisms are not yet understood comprehensively.
UNASSIGNED: The study aimed to use necroptosis-related genes (NRGs) and their relationships with immune-related genes to construct a prognostic signature for OS.
UNASSIGNED: TARGET-OS was used as the training dataset, and GSE 16091 and GSE 21257 were used as the validation datasets. Univariate regression, survival analysis, and Kaplan-Meier curves were used to screen for hub genes. The immune-related targets were screened using immune infiltration assays and immune checkpoints. The results were validated using nomogram and decision curve analyses (DCA).
UNASSIGNED: Using univariate Cox regression analysis, TNFRSF1A was screened from 14 NRGs as an OS prognostic signature. Functional enrichment was analyzed based on the median expression of TNFRSF1A. The prognosis of the TNFRSF1A low-expression group in the Kaplan-Meier curve was notably worse. Immunohistochemistry analysis showed that the number of activated T cells and tumor purity increased considerably. Furthermore, the immune checkpoint lymphocyte activation gene 3 (LAG-3) is a possible target for intervention. The nomogram accurately predicted 1-, 3-, and 5-year survival rates. DCA validated the model (C = 0.669).
UNASSIGNED: TNFRSF1A can be used to elucidate the potential relationship between the immune microenvironment and NRGs in OS pathogenesis.
摘要:
背景:骨肉瘤(OS)是青少年中相对罕见的恶性骨肿瘤;然而,其分子机制尚未全面了解。
目的:本研究旨在利用坏死相关基因(NRGs)及其与免疫相关基因的关系来构建OS的预后标志。
方法:使用TARGET-OS作为训练数据集,GSE16091和GSE21257用作验证数据集。单变量回归,生存分析,和Kaplan-Meier曲线用于筛选中心基因。使用免疫浸润测定和免疫检查点筛选免疫相关靶标。使用列线图和决策曲线分析(DCA)验证结果。
结果:使用单变量Cox回归分析,从14个NRG中筛选TNFRSF1A作为OS预后特征。基于TNFRSF1A的中值表达分析功能富集。Kaplan-Meier曲线中TNFRSF1A低表达组的预后明显较差。免疫组化分析表明,活化的T细胞数量和肿瘤纯度均有显着增加。此外,免疫检查点淋巴细胞激活基因3(LAG-3)是可能的干预靶点.列线图准确预测了1-,3-,5年生存率。DCA对模型进行了验证(C=0.669)。
结论:TNFRSF1A可用于阐明OS发病机制中免疫微环境与NRGs之间的潜在关系。
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